Different sensitivities to acid denaturation within a family of proteins: implications for acid unfolding and membrane translocation.

Colicins A, B, and N form a family of membrane pore-forming toxins with > 50% sequence identity in their toxic C-terminal domains. The colicin A C-terminal domain has been shown to insert into model membranes via an acidic molten-globule insertion intermediate, and thus this family provides a means to compare acid unfolding of related proteins. Unlike the domains of colicins A and B which are acidic, that of colicin N is very basic with fewer Asp and Glu residues. If surface positive charge density is the crucial factor in acidic molten globule formation, colicin N should begin to unfold at higher pH values than colicins A or B. However, comparison of their CD spectra reveals that colicins A and B both form acidic molten globules but colicin N does not. None of the proteins forms a denaturant-induced molten globule at neutral pH where the proteins exhibit very similar stabilities. The acidic unfolding cannot therefore be due to excess positive surface charge and may be caused by a subset of acidic residues as has been predicted for myoglobin. The difference between the colicins is confirmed by their in vivo membrane insertion, with colicins A and B inserting much faster than colicin N. Stopped-flow circular dichroism measurements of colicin A insertion into vesicles confirmed that a molten globule insertion intermediate occurs at the membrane surface.

Placental transfer of milrinone in the nonhuman primate (baboon).

Milrinone is an inotropic agent for short-term intravenous use in the management of congestive heart failure. The purpose of this article is to question the previously reported lack of transplacental transfer of milrinone. Loading and continuous intravenous doses, considered to be therapeutic in humans, were administered to four near-term baboons. Transplacental passage was documented, with a maternal/fetal serum ratio of approximately 4:1 found during the 3 hours of infusion.

Intravenous magnesium sulfate for premature labor: comparison between twin and singleton gestations.

Premature labor occurs frequently in twin gestations, and intravenous magnesium sulfate is commonly prescribed for tocolysis. The purpose of the present investigation was to determine the efficacy and safety of intravenous magnesium sulfate tocolysis in twin gestations using dosing regimens reported for singletons. Outcomes were compared between cases of singleton gestations eligible for tocolysis and admitted immediately before and after each twin case. The standard loading dose in both groups was 4 to 6 g intravenously with a maintenance dose of 1 to 3 g/hr. Data were compared using unpaired t tests or chi-square analysis where appropriate. The 24 evaluable cases of twins were similar in demographics to a similar cohort of 48 singletons. Frequencies of side effects and durations of therapy were the same between the two groups. The number of days from beginning therapy until delivery was highly variable but not significantly different for the twin and singleton groups (13.5 +/- 14.8 vs 20.9 +/- 20.1 days, mean +/- SD). No significant differences were found between the twin and singleton groups in delays in delivery during the first 72 hours (16 [66.7%] vs 35 [72.9%]) and by the 33rd completed week (10 [41.6%] vs 25 [52.1%]). In conclusion, guidelines for prescribing intravenous magnesium sulfate to inhibit premature labor in singletons are equally safe and effective for twin gestations.

Double-blind comparison of intracervical and intravaginal prostaglandin E2 for cervical ripening and induction of labor.

OBJECTIVE: Our purpose was to compare the safety and effectiveness of prostaglandin E2 delivered sequentially as an intracervical (0.5 mg) or intravaginal (2.5 mg) gel. STUDY DESIGN: Hospitalized patients with an unfavorable cervix (Bishop score < or = 4) at > or = 35 weeks and requiring induction of labor were assigned to receive two 2.5 ml doses of gel intracervically and intravaginally in a double-blind, placebo-controlled manner. Second and third doses were given at 6-hour intervals until there were either regular uterine contractions or a Bishop score change > 3 points. RESULTS: The 100 evaluable cases received prostaglandin E2 either intracervically (n = 52) or intravaginally (n = 48). Difficulty with exact gel instillation was present with intracervical gel only, where spillage occurred in 85% of cases. Compared with intracervical therapy prostaglandin E2 given intravaginally was more likely to significantly change the Bishop score (60.4% vs 40.4%, p = 0.04) and stimulate regular contractions (72.9% vs 48.1%, p = 0.01). Uterine hyperstimulation was present in one case in each group. CONCLUSION: Although each was safe, instillation of prostaglandin E2 gel was better at a higher intravaginal dose than a lower intracervical dose because of its greater ease of administration and higher likelihood of cervical change.

Influence of labor and route of delivery on the frequency of respiratory morbidity in term neonates.

OBJECTIVES: The purpose of this study is to compare the frequency of respiratory morbidity (RDS-Type I, RDS-Type II and PFC) in term neonates relative to three different delivery modes (cesarean delivery without labor, cesarean in labor, vaginal delivery). METHODS: A case-control study was performed consisting of 692 maternal/neonate pairs at term gestation with either a documented mature lung profile at an obstetrical age > or = 37 weeks' gestation or a Dubowitz age > or = 38 weeks' gestation. RESULTS: Overall, the frequency of neonatal respiratory morbidity was 5.1%. Neonatal respiratory morbidity was observed in 23 (12.4%) of 186 cases when cesarean delivery was performed prior to the onset of labor; in 10 (5.6%) of 177 cases when the cesarean delivery was performed after labor had ensued; and in 2 (0.6%) of 329 cases when the fetus was delivered vaginally (P < 0.001). CONCLUSION: The frequency of respiratory morbidity in term neonates is influenced by labor and route of delivery, and it is highest when cesarean delivery is performed prior to the onset of labor.